chr12-942329-C-T

Variant names:

• chr12-942329-C-T
• rs2887532
• NM_134424.4:c.-19+7273G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.-19+7273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,200 control chromosomes in the GnomAD database, including 1,582 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1582 hom., cov: 33)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 7 publications found

Genes affected

RAD52 (HGNC:9824): (RAD52 homolog, DNA repair protein) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.-19+7273G>A		intron	N/A	NP_602296.2
	RAD52	NM_001297419.1		c.-18-9253G>A		intron	N/A	NP_001284348.1
	RAD52	NM_001297421.2		c.-46+7273G>A		intron	N/A	NP_001284350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.-19+7273G>A		intron	N/A	ENSP00000351284.3
	RAD52	ENST00000430095.6	TSL:1	c.-18-9253G>A		intron	N/A	ENSP00000387901.2
	RAD52	ENST00000461568.5	TSL:1	n.-19+7277G>A		intron	N/A	ENSP00000436008.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19754 AN: 152082 Hom.: 1583 Cov.: 33

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19751 AN: 152200 Hom.: 1582 Cov.: 33 AF XY: 0.132 AC XY: 9823 AN XY: 74386

African (AFR) AF: 0.0310 AC: 1288 AN: 41570

American (AMR) AF: 0.105 AC: 1598 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.0940 AC: 487 AN: 5182

South Asian (SAS) AF: 0.175 AC: 842 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2525 AN: 10560

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12041 AN: 67996

Other (OTH) AF: 0.131 AC: 277 AN: 2110

Alfa AF: 0.150 Hom.: 262

Bravo AF: 0.115

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2887532; hg19: chr12-1051495;